Antibodies
ZM 447439
- 貨號 Cat. No.
- S1103
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
ZM 447439
ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect againstCDK1/2/4, Plk1, Chk1, etc.
| Size | Price | Stock | Quantity | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||||||||||||
Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect againstCDK1/2/4, Plk1, Chk1, etc. | |||||
|---|---|---|---|---|---|---|
| Targets | Aurora A | Aurora B | ||||
| IC50 | 110 nM | 130 nM [1] | ||||
| In vitro | In vitro, ZM-447439 selectively inhibits recombinant human Aurora A and B with IC50 values of 110 and 130 nM, respectively, while other protein kinases of diverse structural types including the mitotic kinases CDK1 and PLK1 are inhibited with IC50 values >10 μM. [1] Aurora kinase inhibitor, ZM-447439 time- and dose-dependently inhibits the growth of all three cell lines with IC50 values of 3 μM (BON), 0.9 μM (QGP-1) and 3 μM (MIP-101) after 72 hours of continuous exposure. In addition, ZM-447439 potently induces cell apoptosis by promoting DNA fragmentation and caspase 3 and 7 activation, and arrests GEP-NET cells in the G0 /G1and G2/M phase of the cell cycle. [2] In mouse embryo, inhibition of Aurora kinase activity by ZM-447439 results in abnormalities during mitosis by regulating the phosphorylation of histone H3 serine 10 (H3S10Ph) from G2 to metaphase with different perturbations in each embryonic cycle. [3] A recent study shows that ZM-447439 exhibits growth inhibitory and proapoptotic effect on cervical cancer SiHa cells, and enhances the chemosensitivity to cisplatin.[4] | |||||
| In vivo | ||||||
| Features | An Aurora selective ATP-competitive inhibitor. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| In vitro kinase assays | Recombinant Aurora A and B are expressed as NH2-terminal His6-tagged fusion proteins using a baculovirus expression system. Aurora A is purified by affinity chromatography using Ni-NTA agarose, and Aurora B is purified by ion exchange chromatography using CM Sepharose Fast Flow. 1 ng purified recombinant enzyme is added to a reaction cocktail containing 25 mM Tris-HCl, pH 7.5, 12.5 mM KCl, 2.5 mM NaF, 0.6 mM DTT, 6.25 mM MnCl2, 10 μM peptide substrate, 10 μM for Aurora A or 5 μM ATP for Aurora B, and 0.2 μCi γ-[33P]ATP (specific activity ≥2,500 Ci/mmol), and is then incubated at RT for 60 minutes. Reactions are stopped by addition of 20% phosphoric acid, and the products are captured on P30 nitrocellulose filters and assayed for incorporation of 33P with a BetaplateTM counter. No enzyme and no compound control values are used to determine the concentration of ZM447439, which gave 50% inhibition of enzyme activity. Further details are available on request from Nicholas Keen. |
|---|
Cell Assay: [2]
| Cell lines | BON, QGP-1 and MIP-101 cells |
|---|---|
| Concentrations | 0-5 μM |
| Incubation Time | 72 hours |
| Method | Cell number is evaluated by crystal violet staining. In brief, cells in 96-well plates are fixed with 1% glutaraldehyde. Then cells are stained with 0.1% crystal violet. The unbound dye is removed by washing with water. Bound crystal violet is solubilized with 0.2% Triton X-100. Light extinction which increases linearly with the cell number is analyzed at 570 nm using an ELISA reader. |
References
Chemical Information
| Molecular Weight (MW) | 513.59 |
|---|---|
| Formula | C29H31N5O4 |
| CAS No. | 331771-20-1 |
| Storage | 3 years -20℃Powder |
|---|---|
| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 103 mg/mL (200 mM) |
|---|---|---|---|
| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | N-(4-(6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-ylamino)phenyl)benzamide |
|---|
Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.51359 | 5.1359 | 10.2718 | 15.4077 |
Customer Reviews (3)
 Click to enlarge | Rating | |
| Source | Mol Biol Cell, 2011, 22(22), 4227-35. ZM 447439 purchased from Selleck | |
| Method | Flow cytometry | |
| Cell Lines | HeLa Tet-on cells | |
| Concentrations | ||
| Incubation Time | 0-1 h | |
| Results | p31comet depletion did not block mitotic exit induced by Aurora B inhibitor ZM447439. |
Product Citations (4)
CDK1 phosphorylation of YAP promotes mitotic defects and cell motility and is essential for neoplastic transormation. [Yang S, et al. Cancer Res 2013;73(22):6722-33]
Determinants of mitotic catastrophe upon abrogation of the G2 DNA damage checkpoint by UCN-01. [On KF, et al. Mol Cancer Ther 2011;10(5):784-94]
Defining pathways of spindle checkpoint silencing: functional redundancy between Cdc20 ubiquitination and p31comet. [Jia L, et al. Mol Biol Cell 2011;22(22):4227-35]
